Both high and low maternal hemoglobin levels increase neonatal risk

1. In this retrospective cohort study, both low and high early-pregnancy hemoglobin levels were linked to higher rates of severe neonatal morbidity and mortality (SNM-M), stillbirth, and preterm birth before 37 weeks.
2. High hemoglobin, but not low hemoglobin, was associated with increased risk of extreme preterm birth (<32 weeks).

Evidence Rating Level: 2 (Good)

Study Rundown: Most studies on maternal anemia during pregnancy focus on populations in low- and middle-income countries, limiting their applicability to high-income settings with lower rates of nutritional deficiencies, infections, and comorbidities. Nevertheless, iron deficiency anemia remains a preventable public health issue in high-income countries and is associated with higher risks of preterm birth, miscarriage, and other adverse perinatal outcomes. This study evaluated the relationship between maternal hemoglobin concentration in early pregnancy and severe neonatal morbidity and mortality (SNM-M), stillbirth, and preterm birth. Both low and high hemoglobin concentrations were linked to higher rates of SNM-M, a relationship that persisted after adjustment for maternal BMI and hyperemesis gravidarum and when extreme preterm births or birthweights below 1500 g were excluded. Low and high hemoglobin levels were also associated with increased rates of SNM-M or stillbirth. High hemoglobin alone was associated with extreme preterm birth, while both low and high levels increased the risk of preterm birth before 37 weeks. Compared with women with normal hemoglobin and ferritin, only infants of women with normal hemoglobin but low ferritin had higher SNM-M risk. Limitations include a lack of data on iron supplementation before and during pregnancy and potential residual confounding. Nonetheless, these findings suggest that both low and high maternal hemoglobin can adversely affect neonatal outcomes. Future studies should examine neonatal outcomes across a range of hemoglobin levels and determine optimal thresholds for initiating iron therapy.

Click to read this study in AIM

Relevant Reading: Maternal low and high hemoglobin concentrations and associations with adverse maternal and infant health outcomes: an updated global systematic review and meta-analysis

In-Depth [retrospective cohort study]: This retrospective cohort study examined the association between early pregnancy hemoglobin and neonatal outcomes. Data were from the MOMBABY database, covering 98% of births in Ontario, Canada, linked to hemoglobin results from the Ontario Laboratories Information System. Singleton pregnancies in individuals aged 18–60 with hemoglobin measured at 2–12 weeks’ gestation between October 1, 2007, and March 30, 2023, were included. Exclusions were missing hemoglobin, invalid health number, non-residency, pregnancy ending before 20 weeks, or known red blood cell disorder. The primary outcome was severe neonatal morbidity and mortality (SNM-M) up to 27 days, including birth under 32 weeks, birthweight under 1500 g, and other diagnoses or procedures. Secondary outcomes included SNM-M or stillbirth, SNM-M excluding extreme preterm or very low birthweight, and preterm birth under 32 or 37 weeks. The study included 1,100,341 births; mean maternal age was 31 years (standard deviation [SD], 4.9), 44.6% were nulliparous, and 69.7% were Canadian-born or long-term residents. Median hemoglobin was 129 g/L (interquartile range [IQR], 123–135), mean 128.7 g/L (SD, 9.4). A U-shaped association was observed between hemoglobin and SNM-M. Compared with 125 g/L (SNM-M 6.7%), rates were 7.4% at 105 g/L (adjusted risk ratios [aRR], 1.08), 7.1% at 100 g/L (aRR, 1.11), 7.7% at 95 g/L (aRR, 1.14), 9.4% at 90 g/L (aRR, 1.17), 7.0% at 135 g/L (aRR, 1.05), and 8.7% at 150 g/L (aRR, 1.20). Patterns persisted after adjusting for BMI or hyperemesis, or excluding extreme preterm or very low birthweight births. Among 502,172 births with ferritin data, infants of women with hemoglobin ≥110 g/L but ferritin <15 μg/L had higher SNM-M risk (aRR 1.07), while low hemoglobin and low ferritin showed no significant difference (aRR 1.07). Overall, this study suggests that both low and high levels of hemoglobin in early pregnancy may increase risk for SNM-M.

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